Not long ago, a friend told me about his symptoms of depression – trouble sleeping through the night, loss of appetite, forgetfulness, and occasional comments that he might be better off dead. It all sounded like a major depression that could have a good chance of responding to an antidepressant medication, but he was reluctant to take medicines that might “control his mind.” Besides, he had read that getting fit at the gym or running a few laps was all he needed to beat the blues.

I am a big fan of the mental and physical benefits of exercise, but I wasn’t convinced that exercise therapy would be enough to cure my friend’s depression. In the last few years, clinical scientists have been focusing more on the mental benefits of physical exercise. Anyone who has run a 10-K or lifted weights knows first-hand the compelling and immediate sense of endorphin-induced euphoria. We feel uplifted and clear-headed, but is it just a transient state – an effective but temporary treatment for depression?

A few years ago, colleagues from Duke University compared the antidepressant effects of aerobic exercise training to the popular antidepressant medicine sertraline, as well as a placebo sugar pill. They randomized depressed patients to one of the interventions and found that after four months about 40 percent of the subjects were no longer depressed. Those who exercised or received the medicine had higher and comparable response rates, but they were only slightly better than the placebo group. Those who exercised at a moderate level – about 40 minutes three to five days each week – experienced the greatest antidepressant effect. So they interpreted that to mean that exercise was just as good as medicine. And in that particular study, the high placebo response meant that nonspecific influences like patient expectations and the attention from the study personnel during monitoring visits may have caused the therapeutic response.

Exercise not only increases blood flow to the brain, it releases endorphins, the body’s very own natural antidepressant. It also releases other neurotransmitters, like serotonin, which lift mood. In fact, the antidepressant in the study, sertraline, is an SSRI or a selective serotinon reuptake inhibitor – it is thought to exert its effects on body chemistry by increasing the amount of brain serotonin, a chemical that is lowered during depressed mental states. Brain-derived neurotrophic factor, a chemical that promotes brain health and memory, is also reduced in depression, and exercise has been found to elevate levels of this neurotransmitter. Maybe a fitness program could boost my friend’s levels in all these areas, and help his forgetfulness, too. He could only laugh at the idea of having 40 extra minutes three times a week to exercise. His wife was mad enough that he worked 14 hour days as it was.

Multiple systematic clinical trials of antidepressant medications have shown that they are significantly more effective than placebo in relieving symptoms in people with major depression. To determine whether or not somebody has a major depression and will respond to an antidepressant medicine, I often use the mnemonic I learned during my psychiatry residency training, which that reminds me of eight features of major depression: “SIG E CAPS.” “SIG” is an abbreviation doctors use to stand for prescribe; “E” stands for energy; and “CAPS” stands for capsules. Each letter is an abbreviation for one of the symptoms: S—sleep decrease or increase; I—interest loss; G—guilt feelings; E—energy decline; C—concentration impairment; A—appetite change; P—psychomotor disturbance (agitation or slowed movements); and S—suicidal thinking. Patients with three or more of these symptoms generally respond well to antidepressants. My friend had at least five of these symptoms so I was confident he would respond to a trial of medication.

Use of antidepressants got a push back recently from a meta-analysis or a combined analysis of previous studies using another SSRI, Paxil, and an older antidepressant drug, imipramine, in a class known as tricyclics. The study suggested that these drugs may be no better than placebo, but that study had drawbacks: for example, it eliminated other antidepressant medicines and did not include sequential treatments. Many patients do not respond to the first medicine they try but respond very well to a medicine from another drug group.

Research and clinical practice support the idea that antidepressant medicines often work best when combined with non-pharmacological approaches like psychotherapy, support groups, or healthy lifestyle habits. So for my friend, he wouldn’t necessarily have to choose one approach over the other. Since he already seemed predisposed toward exercise, I encouraged him to join a fitness center – his wife would probably come around if he cut back on work a few hours, which might also lower his stress levels and improve his mood. But I also urged him to give medicines a try. If he gave it a few weeks or more – antidepressants often take several weeks to have an effect and the first one may not work – there was an excellent chance that he’d have a good response. Before I could finish my suggestions, his cell phone rang. It was his wife reminding him that he was late for dinner. He had to run off. Perhaps that would be good for his mood, if he kept up a good pace.
Copyright Gary Small, M.D.